微生物的DNA復(fù)制調(diào)控研究一直是當(dāng)代生命科學(xué)最受關(guān)注的前沿領(lǐng)域之一,。近日,，華中農(nóng)業(yè)大學(xué)生命科學(xué)技術(shù)學(xué)院教授何正國帶領(lǐng)的課題組在DNA復(fù)制和細胞周期調(diào)控研究領(lǐng)域取得重要進展。
研究人員發(fā)現(xiàn)了古菌的DNA復(fù)制起始蛋白和DNA聚合酶之間存在物理和功能性的相互作用,，并首次在古菌生命體中闡明了DNA復(fù)制起始和延伸兩個過程之間的分子偶聯(lián)機制,。該項成果發(fā)表在國際學(xué)術(shù)期刊美國《國家科學(xué)院院刊》（PNAS）上。
據(jù)介紹,，DNA等遺傳物質(zhì)的精確復(fù)制是生命現(xiàn)象最本質(zhì)的內(nèi)容,。DNA復(fù)制及細胞周期調(diào)控的紊亂將直接導(dǎo)致人的癌癥、衰老等重要疾病的發(fā)生,。然而,，由于人和高等真核生物的這些遺傳調(diào)控機制相當(dāng)復(fù)雜，目前主要以微生物為模式材料開展相關(guān)的分子機制研究,。
古菌是一種常常生活在極端環(huán)境,，如高溫、高鹽,、極端pH等條件下的特殊生命形式,，有趣的是在這類特殊生物中發(fā)現(xiàn)含有人和高等真核生物的DNA復(fù)制調(diào)控關(guān)鍵酶，因而成為重要的模式材料,。
近幾年,，國外科學(xué)家紛紛轉(zhuǎn)入利用這種特別的古菌作為研究材料，期望加快疾病機制的研究，促進關(guān)鍵調(diào)控基因以及新藥靶的發(fā)現(xiàn),。
何正國課題組經(jīng)過長期研究發(fā)現(xiàn),，古菌的DNA復(fù)制起始蛋白和DNA聚合酶在體內(nèi)和體外都能發(fā)生物理相互作用，同時這些復(fù)制起始蛋白還能雙重調(diào)控DNA聚合酶的核心復(fù)制功能,，這些發(fā)現(xiàn)首次在古菌生命體中建立了DNA復(fù)制起始和延伸兩個關(guān)鍵過程之間的分子偶聯(lián)機制,。鑒于相關(guān)的分子細節(jié)在高等真核生物中仍然沒有被闡明，因此該發(fā)現(xiàn)為最終揭示高等生物的復(fù)雜機制提供重要線索,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS May 12, 2009 vol. 106 no. 19 7792-7797
Archaeal eukaryote-like Orc1/Cdc6 initiators physically interact with DNA polymerase B1 and regulate its functions
Lu Zhang,1, Lei Zhang,1, Yi Liu,1, Shifan Yang, Chunhui Gao, Hongchao Gong, Ying Feng and Zheng-Guo He,2
National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
Archaeal DNA replication machinery represents a core version of that found in eukaryotes. However, the proteins essential for the coordination of origin selection and the functioning of DNA polymerase have not yet been characterized in archaea, and they are still being investigated in eukaryotes. In the current study, the Orc1/Cdc6 (SsoCdc6) proteins from the crenarchaeon Sulfolobus solfataricus were found to physically interact with its DNA polymerase B1 (SsoPolB1). These SsoCdc6 proteins stimulated the DNA-binding ability of SsoPolB1 and differentially regulated both its polymerase and nuclease activities. Furthermore, the proteins also mutually regulated their interactions with SsoPolB1. In addition, SsoPolB1c467, a nuclease domain-deleted mutant of SsoPolB1 defective in DNA binding, retains the ability to physically interact with SsoCdc6 proteins. Its DNA polymerase activity could be stimulated by these proteins. We report on a linkage between the initiator protein Orc1/Cdc6 and DNA polymerase in the archaeon. Our present and previous findings indicate that archaeal Orc1/Cdc6 proteins could potentially play critical roles in the coordination of origin selection and cell-cycle control of replication.
